The exceptional adaptability of insects to diverse food sources is central to their survival and evolutionary success. However, the molecular mechanisms underlying this rapid adaptation remain largely uncharacterized. In this study, adaptive phenotypic, transcriptomic, and metabolomic differences in silkworms fed mulberry leaves versus artificial diets were investigated. The results showed that dietary changes induced enrichment of multiple detoxification pathways in the fat body, midgut, and Malpighian tubules, accompanied by significant accumulation of secondary metabolites and xenobiotics such as flavonoids, terpenoids and saponins in these tissues. Stimulation experiments with nine upregulated metabolites in silkworm BmE cells revealed that most metabolites inhibited cell viability and induced detoxification genes such as GST, UGT and CYP upregulated, with flavonoids like genistein and daidzin exhibiting obvious inductive effects. Among the upregulated genes, GSTd2 frequently responded and was significantly upregulated in artificial diet-fed silkworms. Notably, overexpressing GSTd2 in BmE cells enhanced cell tolerance to genistein and daidzin. Furthermore, silkworms overexpressing GSTd2 showed higher flavonoid tolerance and better adaptability to artificial diets. In conclusion, this study provides valuable genetic targets for improving silkworm rearing efficiency on artificial diets, providing reference to optimize feed formulations and theoretical basis for understanding metabolic adaptation mechanisms to artificial diets in silkworms.
Liu et al. (Sat,) studied this question.